Interior surfaces of passageways, particularly small-bore or capillary tubing, as well as larger diameter pipes, ducts and the like, which may carry liquids, gases, or slurries, are very difficult to clean and to maintain in a clean condition. When the flow path is long and narrow, and more specifically when the length to diameter (l/d) is large, it is difficult to clean the surfaces by conventional liquid phase flushing, because such a long, narrow passageways limit liquid flow velocities by creating a high resistance to flow.
High l/d better describes the intended dimensions of the passageway. As examples, endoscope internal tubing has an l/d of about 500-2000; hemodialyzer hollow fibers have an l/d of about 1000-1500; dental chair tubing has an l/d of about 2000-3000; tubular membranes have an l/d of about 500-1500; piping systems, such as used for dairy, food and painting facilities, have an l/d in the range of 1000-3000; water systems and the like have an l/d of about 500-1500. Tubing diameters that can be cleaned according to the present method are from about 0.2 mm to about 10 cm or more, as long as a sufficient gas supply is made available.
As a result of such high l/d and other geometrical limitations, particularly in the case of small diameter tubing, shear stresses that could aid in the removal of contaminants from such tubing surfaces are limited. Low flow velocities also limit the usefulness of aqueous liquid cleaning solutions and solvents for the same reasons.
Cleaning of small diameter passageways is also difficult because of the nature, adhesion characteristics and solubility of certain types of residues. Fluid passageways which supply water, even purified water, develop bacterial and fungal growth from the water on their interior surfaces, as is well known. Bacteria present in the fluid strongly adhere to tubing surfaces and then grow laterally, forming what is known as biofilm, which can possess an adhesive strength of up to 120 Pascal. Biofilm is apparent to the touch as a slimy film and is composed of both organic residues and the multiplying microorganisms. The bacteria deposit on underlying structural matrices comprising polysaccharides with some peptide moieties, calcium carbonate and other materials which adhere to the surfaces of the passageways. This biofilm must be periodically removed because biofilm is the main cause of high bacterial counts and high levels of endotoxins.
In other situations, when an organic layer strongly adheres to the surface of pipes, tubing or other passageways, similar challenges are presented with respect to removal as in the biofilm case. Examples include organic materials deposited in dairy, food, and beverage equipment, and in the biopharmaceutical industries where the composition of debris in not biofilm.
However, removing biofilm, particles and other undesirable substances from capillary size fluid passageways is quite difficult. The biofilm is strongly adherent to passageway surfaces, whether the surfaces be of natural or synthetic materials. Treatment with chemical agents such as disinfectant and biocidal agents can kill the exposed surface bacteria and so reduce the contribution of the biofilm to the total bacterial count. However, the biofilm matrix structure remains an ideal host for new bacteria to colonize and grow. Thus these treatments are only partially and temporarily effective, and the original levels of bacteria return rapidly, sometimes within hours.
Cleaning of instruments by spraying with water or cleaning solutions is also well known. The spray may be generated by an aerosol can or an atomizing device, but it does not ensure complete cleaning of adherent debris either. Complete cleaning only occurs when the adhesion of the debris is overcome, as by shear stress.
In addition to biofilm, passageways of various medical devices may contain particles of various body tissues, mucous, unclotted or clotted blood or blood components, pathogens, macromolecules, proteins and the like, which are referred to hereinafter as “debris”. It is necessary to remove this debris from the passageways in which it exists.
Hemodialyzers and hemofilters used in kidney dialysis are made of bundles of hollow fibers whose walls are permeable membranes, most commonly having a geometry which is of a tubular shape. They are difficult to clean.
Blood components including proteins, glycoproteins, carbohydrates, cells, platelets and the like are known to adhere to the surfaces of dialyzer materials, including fiber lumens, pore surfaces and resin materials present under the cap of the dialyzer. The adhesive strength of such blood components to dialyzer surfaces is high, and cannot normally be removed with conventional exposure to liquids alone. The difficulty of removing these substances from the dialyzer depends on the chemistry of the reagents used for dialyzer cleaning.
Acid reagents, such as peracetic acid, citric acid or phosphoric acid cause denaturing of blood proteins and make them adhere strongly to dialyzer surfaces. At the same time, these reagents increase the adhesive strength of other blood components. For example dialyzers cleaned or re-processed multiple times with a commercial cleaning solution lose over 50% of their water permeability due to the denaturing of proteins and other blood substances within the pore structure. Further, blood clots accumulate in the dialyzer over several cleaning cycles. Blood clots under the cap regions of a dialyzer are changed to solid, gritty substances that are almost impossible to remove, even with manual scrubbing.
Hemodialyzers, hemofilters and filters used in blood processing or oxygenation in common use comprise about 15,000 hollow fibers enclosed in a housing. Each hollow fiber is about 150-200 microns in the internal lumen diameter. On the dialysate side, a sodium bicarbonate solution is used that flows along the outside of the fibers. Blood flows to the inside of the fibers, exchanging solutes with the dialysate side and removing excess liquids and undesirable materials from blood through a thin membrane layer covering the lumen of the fibers. While low molecular weight solutes such as urea and creatinine, and some middle sized proteins, are removed, the loss of important blood proteins, such as albumin, is prevented. The effectiveness of this process is a function of the available membrane surface area that permits blood-dialysate solute exchange; it is estimated by the total cell volume (TCV), i.e., the volume of liquid that fills the available fibers. A typical TCV is about 110-120 ml for adults, and a blood cleaning dialysis treatment is delivered in about three hours. A patient uses a dialyzer, which is cleaned after each session, until it fails, or when the TCV is reduced to less than 80% of its value when new.
At present a hemodialyzer is sterilized with a liquid sterilant such as peracetic acid, formaldehyde, glutaraldehyde and the like, and stored for at least 13 hours. Because it is difficult to maintain a high TCV level and retain the pore size distribution in a re-used dialyzer at about the same level as a new one, only about 10-15 re-processings, and often fewer, can be carried out prior to failure, when the dialyzer must be discarded.
Blood clots that form inside the hollow fibers clog some of them, reducing the TCV; also blood clots form particularly in regions under the cap of the dialyzer. Protein layers also form on the lumen of hollow fibers which can hamper the removal of undesirable solutes from the patient's blood to the dialysate or liquid side. Precipitation of proteins and other molecules within the pore structure also clog the pores. Thus reprocessing or cleaning of the dialyzers is very important but has not been sufficiently addressed. Instead, up till now, the emphasis has been on preventing microbial infections by sterilization of the used dialyzers, while ignoring the clearance of undesirable solutes during dialysis treatment.
The most commonly used reprocessing solution is a peracetic acid sterilant available as Renalin®, a peracetic acid-hydrogen peroxide mixture available from the Minntech Corporation of Minneapolis, Minn. However, this solution, although it sterilizes the hemodialyzer, does not clean the pores by removing proteins, blood clots and the like, and does not clean under the cap regions adequately, where blood clots and other material tends to aggregate. Thus the dialyzers become fouled, limiting their number of re-uses, compromising dialysis treatment of patients, and raising the cost of dialysis because new dialyzers must be provided more frequently.
Another method in common use to reprocess hemodialyzers uses 0.5-1.0% hypochlorite bleach for cleaning. This is generally done by backflushing the bleach solution by pressurizing the dialysate compartment for a short time, followed by rinsing with water and filling the dialyzer, either with formaldehyde or glutaraldehyde sterilants. Although in principle this method should clean the pores, it is not effective to remove blood clots from the fiber lumen or from the under the cap regions of the dialyzer. Although this method is more effective in removing protein residues from the dialyzer, the number of times a dialyzer can be reprocessed is about the same as using the Renalin® method. Further, bleach increases the pore size and effects a shift in the pore size distribution in the membrane layer, leading to high loss of albumin in patients. This has been found to be the main cause of albumin loss in hemodialysis patients, which has an adverse effect on their health.
In response, the industry has re-formulated the composition of the membrane layer and introduced two types of polysulfone-based hemodialyzers—one for use with bleach reprocessing, and the other for use with peracetic acid. However, despite some improvements in dialyzer materials, albumin loss in patients remains a major issue with respect to the number of possible re-uses. Further, the bleach solution method is not efficient in maintaining the TCV above the 80% level of that of a new dialyzer, and maintaining the dialyzer in good functional condition for many re-uses.
Another recent cleaning method is based on citric acid, followed by preserving the dialyzers at high temperature to ensure disinfection. However, due to the low pH of citric acid solutions, protein layers deposited on the lumen surface of hollow fibers precipitate inside the pore structure of the membrane layer and are not removed by this processing method. The method does not adequately clean, and the prolonged elevated temperatures of disinfection leads to shell fatigue. Thus inadequate cleaning and the cost of energy to sterilize the dialyzer are major drawbacks to this method.
Still another method for reprocessing is by circulating hot water on a continuous basis between dialysis sessions. Again, only visible blood is removed. Maintaining the dialyzer at elevated temperatures denatures proteins in the blood, which remain in the lumen and pore structure, impairing clearance of middle solutes such as β2-microglobulin (hereinafter beta-2M) during dialysis.
The clearance of beta-2M from patient blood during dialysis takes place by two mechanisms, ultrafiltration and adsorption onyo the surface of pore structures. Existing dialyzer reprocessing methods cannot achieve the desired clearance of beta-2M and other undesirable molecules because of the loww of pore volume due to precipitated proteins in the pore structure and by masking the polymer surface of the dialyzer fibers with a protein layer, that diminishes removal of such molecules by adsorption. The present method does achieve the removal of protein pore structure and of all surfaces, thus increasing the coefficient of ultrafiltration and the capacity of adsorption.
Another major limitation in existing reprocessing methods lies in their inability to equally clean both venous and arterial sides of the dialyzers. This differential fouling problem is caused by the fact that the dialyzer is mounted in one direction during dialysis treatment. Since the dialysate is pumped in the reverse direction to blood flow from the arterial side, a low pressure between the dialysate and blood compartments always exists at the venous side of the dialyzer. This results in more severe fouling of the hollow fiber lumen and pore structure on the venous side. None of the current reprocessing methods addresses this major problem.
In summary, none of the present cleaning methods can remove blood clots from hollow fibers and from under the cap areas of a dialyzer; remove accumulated protein deposits formed on the surface of the fiber lumen; remove protein and other biological materials from the pore structure of the dialyser; perform equivalent cleaning of the arterial and the venous sides of the dialyser; keep the dialyzer in such condition that it can effectively remove middle solutes such as beta-2M; nor increase the number of reuses while delivering optimum performance of the dialyzers, thereby achieving the best dialysis treatment of patients without compromise.
Another objectionable feature of present-day dialyzer cleaning, is the potential exposure of dialyzer reprocessing workers to infection and other consequences, since the cleaning operation often involves opening the dialyzer caps to manually remove blood clots from under the cap.
The present methods do not clean the dialyzer of protein deposits or other residues, and thus are deficient in that the required treatment function is not delivered to the patient, and the costs of treatment are increased.
Other suggestions for cleaning have been made, but they have proven to be no more effective in cleaning, and some have other problems as well.
Thus a method of cleaning and sterilizing dialyzers, including fiber lumen, pore structure, under the cap regions and fouling on both the arterial and venous sides, and of increasing the number of reuses, bringing the properties of the dialyzer close to a new one, would be highly desirable.